The noradrenergic system in brain has been implicated as playing a role in a wide variety of normal behavioral and abnormal psychiatric states. Many of the drugs used in psychiatry are presumed to act by mechanisms involving the central noradrenergic system. The mechanisms of drug action in brain, however, are based mainly on analogy with pharmacological actions in the peripheral noradrenergic (sympathetic) system. Functional mechanisms and pharmacological action within the brain itself are poorly understood. In these investigations, the aim is to demonstrate two specific functions of the noradrenergic system in brain and to define how these functions can be affected pharmacologically. These functions have been hypothesized on the basis of anatomical findings made using immunofluorescence localization of the enzyme dopamine-Beta-hydroxylase. (The enzyme that catalyzes the conversion of dopamine to norepinephrine.) These two functions are (1) effects of the central noradrenergic system on cerebral microcirculation; (2) effects of the central noradrenergic system on the neurosecretory function of the supraoptic nuclei. These functions will be systematically studied using two basic methods: (1) effects of selective destruction of the central noradrenergic system using intraventricular and stereotactially injected doses of 6- hydroxydopamine; and, (2) use of centrally administered drugs that have been shown to affect the centrally noradrenergic system in preliminary experiments and drugs that have been postulated to affect this system. Microcirculatory function will be evaluated in monkeys by residue detection of oxygen-15 labelled water and in rats by double- label radio isotope experiments measuring the ratio of brain uptake of test substances relative to a standard. Neurosecretion of antidiuretic hormone by the supraoptic nucleus will be evaluated indirectly using physiological tolerance tests and directly using radioimmunoassay. Information obtained by focusing on these relatively non-complex but well defined and measurable functions will serve as a basis for investigation of more complex functions of the central noradrenergic system.